6x2p

Crystal Structure of the Mek1NES peptide bound to CRM1Crystal Structure of the Mek1NES peptide bound to CRM1

Structural highlights 6x2p is a 4 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.401Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function XPO1_YEAST Receptor for the leucine-rich nuclear export signal (NES). Publication Abstract from PubMed The E571K mutation of CRM1 is highly prevalent in some cancers, but its mechanism of tumorigenesis is unclear. Glu571 of CRM1 is located in its NES-binding groove, suggesting binding of select NESs may be altered. We generated HEK-293 cells with either monoallelic CRM1WT/E571K or biallelic CRM1E571K/E571K using CRISPR/Cas9. We also combined analysis of binding affinities and structures of 27 diverse NESs for wild-type and E571K CRM1 with structure-based bioinformatics. While most NESs bind the two CRM1 similarly, NESs from Mek1, eIF4E-transporter and RPS2 showed >10-fold affinity differences. These NESs have multiple charged side chains binding close to CRM1 position 571, but this feature alone was not sufficient to predict different binding to CRM1(E571K). Consistent with eIF4E-transporterNES binding weaker to CRM1(E571K), eIF4E-transporter was mislocalized in tumor cells carrying CRM1(E571K). This serves as proof of concept that understanding how CRM1(E571K) affects NES-binding provides a platform for identifying cargos that are mislocalized in cancer upon CRM1 mutation. Lastly, we showed that large affinity changes seen with some NES peptides (of Mek1 and RPS2) do not always translate to the full-length cargos suggesting limitations with current NES prediction methods. Therefore, comprehensive studies like ours are imperative to identify CRM1 cargos with real pathogenic potential. Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation.,Baumhardt JM, Walker JS, Lee Y, Shakya B, Brautigam CA, Lapalombella R, Grishin N, Chook YM Mol Biol Cell. 2020 Jun 10:mbcE20040233. doi: 10.1091/mbc.E20-04-0233. PMID:32520643 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Exportin 3D structures GTP-binding protein 3D structures

spinqualitylabelsall models 6x2p, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image